The effects of beta 1-adrenoceptor partial agonist ICI 118.587 on left ventricular function in patients with coronary heart disease

We investigated the effects of a new selective beta 1-adrenoceptor partial agonist, ICI 118.587, on left ventricular function in 14 patients with coronary heart disease and a history of stable angina pectoris. The drug (0.2 mg/kg) increased peak left ventricular dp/dt from 1518 to 1993 mm Hg/sec (P less than 0.001) and left ventricular Vmax from 1.63 to 2.08 circ/sec (P less than 0.001), while left ventricular end-diastolic pressure decreased (P less than 0.05). Measured by echocardiography, the fractional shortening of the left ventricular minor axis diameter and the mean velocity of the left ventricular circumferential fiber shortening increased (P less than 0.001) and the cardiac index increased by 36%, reflecting increased contractility mainly in the normal left ventricular wall areas. In coronary heart disease, ICI 118.587 increased left ventricular muscle contractility and output without untoward side effects in the majority of the patients.     

Pharmacokinetics of digoxin in patients with acute myocardial infarction.

The effects of acute myocardial infarction on the pharmacokinetics of digoxin were studied. Digoxin, 0.75 mg, was given orally to 12 patients with left-sided cardiac failure due to acute myocardial infarction and to 9 healthy control subjects. Serum concentration of digoxin in the first 4 hours and the area under the serum concentration-time curve in the first 12 hours after administration of the drug were lower in patients with infarction than in control subjects (P less than 0.01). The 24 hour area under the concentration curve, the amount excreted in urine and the renal clearance did not differ between the groups. The 24 hour area under the concentration curve correlated with the predigoxin pulmonary capillary wedge pressure and with heart rate (P less than 0.01). The decrease of renal clearance of digoxin was related to the serum activity of MB isoenzyme of creatine kinase (P less than 0.001). Morphine reduced and delayed the peak serum concentrations of digoxin (P less than 0.001). Thus, the absorption of oral digoxin was slower and the peak concentrations remained lower in patients with acute myocardial infarction than in healthy control subjects. However, the total amount of digoxin absorbed was unchanged.     

Noninvasive evaluation of the athletic heart: sprinters versus endurance runners.

To evaluate possible differences in the cardiac effects of different types of running training, 22 competing male runners--10 sprinters and 12 endurance runners--were studied with a physical examination, electrocardiography, chest X-ray film and echocardiography. Thirteen sedentary men served as control subjects. There were no differences between the athletic groups in physical findings. However, left ventricular hypertrophy in the electrocardiogram was more apparent in the endurance runners (P less than 0.05), whose relative heart size on chest X-ray examination was also greater than in the sprinters (P less than 0.02). On echocardiography the left ventricular end-diastolic volume was equally greater than normal in both groups of athletes (P less than 0.005), but in the endurance runners the percent chance of the minor axis diameter in systole was greater than in the sprinters or control subjects (P less than 0.02). Values for left ventricular wall thickness and mass were greater than normal in both groups of athletes but were higher in the endurance runners than in the sprinters (P less than 0.001). The left atrial diameter was apparently greater in the endurance runners than in the sprinters or control subjects (P less than 0.001), whereas that of the sprinters did not differ from normal. Thus, intensive sprinter training seems to dilate the left ventricle but causes less increase in wall thickness and mass than training for endurance running and no change in left ventricular function or left atrial size. Endurance running causes left ventricular dilatation equal to that of sprinter training, greater wall hypertrophy and improved systolic emptying of the left ventricle, and it also dilates the left atrium perhaps because of decreased left ventricular compliance.     

Effect of coronary artery bypass grafting on left ventricular response to isometric exercise

The left ventricular (LV) response to isometric exercise was evaluated in 20 patients who performed handgrip exercise tests before and 3 months after coronary artery bypass grafting. Preoperative LV ejection fraction (EF) decreased during the handgrip test from 0.57 +/- 0.08 to 0.49 +/- 0.09 (p less than 0.001); the ratio between the LV peak systolic pressure (PSP) and end-systolic volume index (ESVI) did not change. In 12 patients with patent grafts, the LVEF after operation did not change (0.54 +/- 0.06 at rest and 0.56 +/- 0.06 during handgrip exercise) and PSP/ESVI ratio increased from 4.5 +/- 1.5 to 5.6 +/- 2.1 mm Hg/ml X m-2 (p less than 0.001) during exercise. In 8 patients with occluded grafts, the LVEF after operation decreased from 0.56 +/- 0.10 to 0.48 +/- 0.06 (p less than 0.02), whereas PSP/ESVI did not change during handgrip exercise. Thus, the LV response to isometric handgrip exercise appears to improve after coronary artery bypass grafting in patients with patent grafts, but not in patients with 1 or more occluded grafts.     

Coronary arteriography and left ventriculography during spontaneous and exercise-induced ST segment elevation in patients with variant angina

The present study is an angiographic demonstration of coronary artery spasm during both spontaneous and exercise-induced angina in three patients with variant angina. In each case, clinical, ECG, coronary angiographic, and left ventriculographic observations were made at rest, during spontaneous angina, and during exercise-induced angina. The character of chest pain was similar during spontaneous and exercise-induced episodes. ST segment elevation was present in the anterior ECG leads during both episodes. The left anterior descending coronary artery became partially or totally obstructed during both types of attacks. When coronary spasm was demonstrated during both types of attacks, left ventriculography disclosed akinetic or dyskinetic wall motion in the area supplied by the involved artery. In those patients with reproducible exercise-induced ST segment elevation and chest pain, thallium-201 scintigraphy showed areas of reversible anteroseptal hypoperfusion. Thus in selected patients exercise-induced attacks of angina were similar to spontaneous episodes.     

Cardiac venous blood flow in atrial pacing versus exercise-induced angina pectoris

Thirteen patients with angina pectoris underwent measurements of great cardiac vein blood flow at rest, with the onset of angina pectoris induced by atrial pacing, and again during angina pectoris induced by exercise in order to compare the regional coronary blood flow response to differing myocardial stresses. All patients had significant obstructions of the left anterior descending artery.Exercise-induced angina, compared to pacing-induced angina, was associated with a higher systolic pressure, higher left ventricular end-diastolic pressure, and a lower heart rate. Indices of myocardial oxygen demand, that is, the systolic pressure-heart rate product and the tension-time index, increased to a similar degree during both types of myocardial stress and great cardiac vein blood flow paralleled these changes.We conclude that in a given patient the level of regional coronary blood flow is similar at the onset of either pacing- or exercise-induced angina, despite significant differences in the hemodynamic response to these myocardial stresses.     

Postnatal development and sex differences in hepatic phosphatidate phosphohydrolase activity in the rat

The mechanism leading to the difference in hepatic triacylglycerol metabolism between female and male rats was investigated by studying the ontogeny of hepatic soluble phosphatidate phosphohydrolase activity in feeding animals of both sexes. A sevenfold increase occurred within 12 hr of birth, returning to the adult level during the third postnatal day. The changes in enzyme activity were followed by similar changes in hepatic triacylglycerol concentrations. A sex difference was observed only in the adult rats, where the enzyme activity in the livers of feeding female rats was about 25% higher than that in the feeding males. The effects of gonadectomy and sex steroids were studied in a separate series of experiments on fasting animals. The activity of the soluble enzyme was 65% higher in the intact female rats than in the males, and that of the microsomal enzyme 130% higher. The activity ratio between the soluble and microsomal enzyme in the male rats was 4.3 on a liver wet weight basis with the methods used. Gonadectomy increased the soluble and microsomal activities by 25% and 80% respectively within 6 wk in the male rats. The soluble and microsomal activities were still at the same control levels 2 wk after the gonadectomy, the subcutaneous implants of testosterone or estradiol resulting in 10-fold increases in plasma hormone levels had no effects on these enzyme activities, although testosterone caused 50% decrease in the hepatic triacylglycerol concentration. These data indicate that, if hormonally mediated, the postnatal increase in phosphatidate phosphohydrolase activities is not related to sex steroids and also suggest that the basis of the sex difference in hepatic soluble phosphatidate phosphohydrolase activity remains to be established.     

Angina pectoris, myocardial infarction and sudden cardiac death with normal coronary arteries: a clinicopathologic study of 9 patients with progressive systemic sclerosis

The syndrome of angina pectoris or acute myocardial infarction without obstructive coronary artery disease has been the subject of much interest. We studied nine autopsied patients with progressive systemic sclerosis and evidence of ischemic heart disease but morphologically normal coronary arteries. Three patients had angina pectoris and three others chest pains of unknown etiology, six had ventricular arrhythmias, four had clinically suspected acute myocardial infarction, and eight had sudden cardiac death. At autopsy extensive focal myocardial necrosis was present in seven patients and myocardial scarring in all nine, but all patients had widely patent intramural and extramural coronary arteries. The finding of contraction band myocardial necrosis in seven of the eight patients who experienced sudden death suggests that the myocardial damage was a consequence of reperfusion of focally nonperfused myocardium, and thus due to a myocardial Raynaud's phenomenon. Patients with PSS may provide a model of spasm of intramyocardial vessels causing angina pectoris or myocardial infarction with morphologically normal coronary arteries.     

Changes in the QRS complex and ST segment in transmural and subendocardial myocardial infarctions. A clinicopathologic study.

The QRS complex and ST segment in the ECGs of 80 patients who died of an acute myocardial infarction (MI) were studied in relation to the extent of the MI (subendocardial vs. transmural). Changes in the QRS complex developed in nine out of the 15 cases with an acute subendocardial MI. Five of these cases fulfilled the conventional QRS criteria for a myocardial infarction. A definite ST segment depression (a J point depression of 2 mm. or more in at least one lead, and a horizontal or downward sloping ST segment with a minimum duration of 0.08 sec.) occurred most frequently in connection with a circumferential subendocardial MI (88 per cent), but it was also found in a regional subendocardial (43 per cent) and transmural MI (43 per cent). In 17 per cent of the cases with a transmural MI, this was the only ECG abnormality. It is concluded that cases with a subendocardial MI cannot always be distinguished from transmural MI on the basis of the presence or absence of the QRS changes, and that an ST segment depression, as defined in this study, can give additional information in the evaluation of an acute phase of an MI.     

Left ventricular response to isometric exercise and its value in predicting the change in ventricular function after mitral valve replacement for mitral regurgitation

Reduced left ventricular (LV) afterload and its effect on the resting ejection fraction may lead to over-estimation of LV function in mitral regurgitation (MR). To evaluate LV function during increased afterload of the heart, an isometric handgrip test was performed during cardiac catheterization in 15 patients with mitral regurgitation (MR group) and in 9 normal subjects (normal group). Twelve months after successful mitral valve replacement (MVR) the patients were recatheterized, and the value of preoperative stress testing in predicting the change in resting ventricular function after surgery was estimated.Isometric exercise caused an increase in end-systolic wall stress, a measure of ventricular afterload, in both the MR group and the control group (p < 0.001). The ejection fraction remained unchanged in the control group, but decreased from 0.58 ± 0.08 to 0.53 ± 0.08 in the MR group (p < 0.001). After MVR, end-systolic wall stress increased significantly (p < 0.001) and the ejection fraction decreased from 0.58 ± 0.05 to 0.51 ± 0.1 (p < 0.05). A positive correlation existed between the change in the ejection fraction during preoperative stress testing and the change in the resting ejection fraction after MVR (r = 0.65, p < 0.01). In 8 patients whose resting ejection fraction was within normal limits (> 0.55) preoperatively, the ejection fraction was depressed (< 0.55) 1 year after surgery. In all but 1 of these patients the isometric exercise revealed the reduced ventricular response to afterload stress preoperatively (decrease of the ejection fraction > 0.03 during exercise). Therefore, the isometric exercise-induced change in LV function appears to predict the influence of MVR on LV function.     

Regional coronary angiographic observations during cold stimulation in patients with exertional chest pain: Comparison of diameter responses in normal and fixed stenotic vessels

In 12 patients with exertional chest pain, coronary angiography was periormed and quantitative measurements of coronary artery (CA) diameters were made before and during cold stimulation (four normal CA patients and eight fixed CA stenosis patients). The left main CA; proximal, middie and distal anterior descending and circumflex segments; and small intramyocardial CAs (0.4 to 1.0 mm) usually showed only minimal and similar degree of vasoconstriction (average diameter reduction 6%) during cold stimulation in both normals and CA disease (CAD) patients. Magnitude of vasoconstriction differed among some CA segments measured; the left main CA segment (0 ± 2%, mean ± SD) usually did not change while distal segments (?10 ± 10%) usually demonstrated greatest percentage vasoconstriction. Coronary stenoses and CAs filled by collaterais did not demonstrate increased magnitude of vasoconstriction compared to other CAs. Results of other CA segments were also similar comparing patients with and without CAD. The minimal degree of vasoconstriction observed in these CA segments does not appear to account for the large increase in coronary resistance reported during cold stimulation in CAD patients.     

Coronary anatomy and arteriography in patients with unstable angina pectoris.

A prospective series of 188 patients with the syndrome of unstable angina pectoris undergoing coronary arteriography was reviewed to determine the spectrum of anatomic coronary artery disease, suitability for coronary revascularization and in-hospital morbidity and mortality. Thirty-two patients demonstrated normal to moderately diseased coronary arteries. None of these patients sustained myocardial infarction or died. Twenty patients (10.6 percent) had normal coronary arteriograms. Of the 156 patients having severe coronary artery disease (greater than 70 percent stenosis), 20 patients (13 percent) had left main coronary artery disease. One hundred forty-two patients (91 percent) were potential candidates for coronary surgery; 14 were not candidates because of distal vessel disease or poor left ventricular function. During cardiac angiography or in the subsequent hospital period 12 patients sustained a myocardial infarction and 7 of these died. Of these seven, six had left main coronary artery disease and one had three vessel disease. In three patients who died (1.9 percent of those with severe coronary artery disease) the death may have been related to cardiac catheterization because evidence of myocardial necrosis began within 24 hours of study. Thus, patients with the syndrome of unstable angina pectoris usually presented with severe coronary artery disease and were candidates for coronary revascularization. The anatomic severity of coronary artery disease appeared to be the most important factor contributing to myocardlal infarction or death after cardiac catheterization. Mortality after catheterization was primarily associated with left main coronary artery disease.     

Prognostic significance of an ST segment depression of patients with an acute coronary attack

An ST-segment depression was studied in the ECGs recorded on the first and third day after admission of 580 patients with an acute heart attack. An acute myocardial infarction was found in 86% of the 115 patients in whose ECG the J-point was depressed 2 mm. or more and the ST-segment was horizontal or sloping downwards in at least one lead (a definite ST-segment depression).The degree of the J-point depression was deemed of prognostic significance. During the first four weeks, the mortality rate was lowest (4.7%) in patients with a J-point depression less than one millimeter or no depression. The corresponding figure for patients with a definite ST-segment depression was three times (21.7%) that of the patients without the pattern (7.3%).The definite ST-segment depression in an acute coronary attack seemed to be accompanied by a severe degree of coronary heart disease. Significant differences between the patients with a definite ST-segment depression and those without the pattern were found in the $\text{C}\text{T}$ ratio, in the degree of pulmonary congestion, in the ECG signs of LVH, and in the digitalis treatment.It is concluded that the definite ST-segment depression has an important clinical and prognostic significance in cases of acute coronary attacks.     

Evaluation of systolic time intervals in patients with angina pectoris

We have explored the systolic time intervals of 52 patients with angina pectoris at the time of their hospitalization in our wards. Our results are in close agreement with published data, essentially indicating prolongation of the preejection time and shortening of the ejection time. These alterations of systolic times can be interpreted pathophysiologically as as expressing reduced myocardial contractility. The long PEP-short LVET polygraph picture, occurring in the course of chronic ischemic heart disease, reveals the deficit of myocardial contractility at a stage of the disease at which clinical evidence of left ventricular failure is usually not yet detectable.     

Electrocardiographic responses to atrial pacing and multistage treadmill exercise testing. Correlation with coronary arteriography

Atrial pacing was compared with multistage treadmill exercise testing in 50 patients undergoing diagnostic cardiac catheterization to determine the diagnostic sensitivity of atrial pacing. Coronary artery disease was considered significant if luminal narrowing greater than 75 percent was present. Twenty-one subjects (Group I) had no significant coronary artery disease with vessel narrowing of less than 50 percent. Twelve (Group II) had single vessel disease and 17 (Group III) had disease of two or more vessels.The mean maximal heart rate during atrial pacing was 140/min and during exercise testing was 131/min. A positive atrial pacing test result was obtained in 5 percent of patients in Group I, 17 percent of patients in Group II and 24 percent of patients in Group III. A positive multistage treadmill exercise test result was obtained in 10 percent of patients in Group I, 67 percent of patients in Group II and 94 percent of patients in Group III. These differences are statistically significant (P < 0.001). The sensitivity of atrial pacing was 20 percent compared with 83 percent for multistage treadmill exercise testing. The specificity of atrial pacing was 95 percent compared with 90 percent for multistage treadmill exercise testing. Thus, atrial pacing is an insensitive test in the diagnosis of ischemic heart disease and does not improve the diagnostic value of multistage treadmill exercise testing.     

Prevalence and significance of reversible radionuclide ischemic perfusion defects in symptomatic aortic valve disease patients with or without concomitant coronary disease

To determine the prevalence and significance of exercise-induced localized perfusion defects in symptomatic patients with aortic valve disease, thallium-201 rest and exercise studies were performed in a consecutive series of 29 such patients prior to left heart catheterization with coronary arteriography. Eight patients had repeat studies after aortic valve replacement. Twelve of 17 patients with predominant aortic regurgitation (AR) had distinct LV apical defects during exercise despite normal coronary arteries, while 10 of 12 patients with aortic valve disease and associated coronary artery disease (CAD) had localized perfusion defects in LV areas other than the apex. In patients with AR, reversible apical perfusion defects can occur without CAD; these apical detects are probably a reflection of severe LV volume overload in AR. LV perfusion defects in areas other than the apex are specific for CAD in aortic valve disease, and concomitant CAD may not provoke regional LV perfusion deficits in aortic stenosis patients with severe LV hypertrophy.